NIH study faulted for failing to disclose risks

Mark Greenblatt, Scripps News

10:45 PM, May 19, 2014

Top U.S. health officials inappropriately influenced a federal inquiry into alleged ethical blunders involving a major National Institutes of Health study of premature infants, according to the Washington-based watchdog group Public Citizen.

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Photo by Dan Kitwood/Getty Images

WASHINGTON, D.C. - Top U.S. health officials inappropriately influenced a federal inquiry into alleged ethical blunders involving a major National Institutes of Health study of premature infants, according to the Washington-based watchdog group Public Citizen.

More than 400 pages of heavily redacted emails obtained by Public Citizen appear to show that officials in the Department of Health and Human Services permitted NIH Director Francis Collins and others to review and edit investigative findings by the Office for Human Research Protections. The OHRP is supposed to work as an independent oversight group to help assure safe, ethical standards in medical research.

The NIH study was criticized early last year for failing to notify parents of possible health risks to more than 1,300 babies. The research resulted in a higher death rate than NIH expected for some infants.

Teaming up investigators with the departments under scrutiny is "one of the biggest ethical lapses in the history of the National Institutes of Health," said Dr. Michael Carome, director of Public Citizen's Health Research Group. Carome, a physician and former compliance director of the OHRP, retired from the government in 2010 after more than 24 years in federal health agency jobs.

With the NIH conducting thousands of medical studies on people every year, Carome said, "we need a robust office that oversees the ethics of these trials independently, without interference from NIH."

"Most troubling, it appears that numerous officials at the very highest levels of HHS were aware of this interference," DeLauro wrote.

The inspector general's office confirmed that Public Citizen's 34-page request for an investigation arrived late Monday afternoon."We did receive the letter and are studying it carefully," said Donald White, spokesperson for HHS OIG.

Public Citizen says that the experimental study exposed premature infants to increased risk of blindness, brain injury and death without fully informing parents of the risks or the true nature and purpose of the research. In some cases, parents were told the experimental procedures "essentially had no risk," according to Public Citizen.

The study sought to identify the proper oxygen levels required to minimize blindness and other complications. Infants were provided amounts of oxygen within ranges that NIH believed to be safe at the time. Critics later noted that earlier research pointed to potential risks that should have been disclosed to parents.

The project, known as the SUPPORT study, was funded by the NIH and conducted at more than 20 medical centers around the country, including the Yale-New Haven Children's Hospital, the Lucile Packard Children's Hospital at Stanford, and the Duke University School of Medicine.

In a letter dated March 7, 2013, the investigators at OHRP seemed to agree with the criticism. They concluded that the project's consent form failed to make clear to parents that lower levels of oxygen given to some infants in the study could increase the risk of injury or death. The 13-page letter to Richard B. Marchase, vice president for Research & Economic Development at the University of Alabama at Birmingham, the study's lead research site, requested a response and a correction plan.

The initial emails in the months that followed suggest a growing concern as the review became a front burner issue for top health officials.

Follow the discussion between health officials below. The following documents have been excerpted from over 400 pages of emails.

Beginning in April 2013, emails on the issue were coded of "high" importance. Within days, officials were organizing conference calls directly with investigators at OHRP.

Over the next weeks, the emails suggest increasingly close collaboration in shaping the investigators' views. On May 1, NIH Director Francis Collins told Deputy HHS Secretary Bill Corr that he had been closely tracking the progress and his staff was working with the regulators to develop a "consensus set of statements that OHRP could put forward." Two days later, OHRP Director Jerry Menikoff sent to HHS what he described as a "revised version."

A group of HHS officials held a Saturday conference call, and Kathy Hudson, NIH's Deputy Director for Science, Outreach and Policy later circulated an email of "the edits we discussed." One message mentions issues NIH is working on "collaboratively" with OHRP. Another refers to "edits" made by HHS Assistant Secretary Howard Koh.

"It is not necessary to disclose all theoretical risks present at the outset of every study," wrote Lisa Buchanan, OHRP's Compliance Oversight Coordinator. Regulators, she added, had put a hold on all compliance actions regarding the study and planned to take no action on similar studies until "appropriate guidance" was in place.

The National Institutes of Health declined to comment, deferring to the Department of Health and Human Services.

"OHRP regularly works with entities such as NIH ... and others to ensure the protection of human subjects in research," an HHS spokesperson said in an email. The regulators "became aware of different understandings" about which risks must be disclosed to potential research subjects, said the spokesperson. OHRP is "currently drafting guidance on the issue."

Neither HHS nor NIH would answer questions about the appropriateness of the emails or alleged conflicts of interest.

The NIH has faced concerns about cozy relationships with regulators before.

At one time, an oversight group for human research reported directly to NIH. But after a 1996 federal audit called for more independence, the department was dissolved and replaced by the OHRP. It reports to HHS.